NORD gratefully acknowledges James E. Heubi, MD, Professor and Associate Chair for Clinical Research of Pediatrics, Associate Dean for Clinical and Translational Research, Children's Hospital Medical Center /University of Cincinnati College of Medicine, for assistance in the preparation of this report.
Reye syndrome is a rare disorder of childhood and adolescence. It primarily affects individuals under 18 years of age
Synonyms of Reye Syndrome
The specific cause of Reye syndrome remains unknown. However, according to researchers, there appears to be an association between the condition's onset and the administration of aspirin-containing medications (salicylates) in children or adolescents with certain viral illnesses. This typically includes upper respiratory tract infections caused by the influenza B virus or chickenpox (varicella). Less commonly, the development of Reye Syndrome has been reported in association with other viral infections, including influenza A, herpes simplex, rubella, or Epstein-Barr.
The primary symptoms and findings associated with Reye syndrome appear to result from distinctive, fatty changes of the liver, impaired liver functioning, and an abnormal accumulation of fluid in brain tissues (cerebral edema), which may lead to increased fluid pressure and potential compression of brain tissue. In individuals with Reye Syndrome, degenerative changes of the liver are associated with an abnormal infiltration of liver cells (hepatocytes) with fatty compounds (e.g., triglycerides). In addition, to a lesser degree, there may be fatty infiltration of the spleen, the pancreas, voluntary (skeletal) muscles, heart muscle (myocardium), and/or the tubular structures within the kidneys that collect and conduct urine (renal tubules).
Researchers suggest that the primary underlying defect in Reye syndrome is abnormal functioning of mitochondria with reduced activities of liver (hepatic) mitochondrial enzymes (e.g., ornithine transcarbamylase [OTC], carbamyl phosphate synthetase [CPS], pyruvate dehydrogenase [PDH]). However, the cause of such mitochondrial dysfunction remains unknown. Mitochondria are the tiny, rodlike structures (organelles) outside the nuclei of cells that function in cellular metabolism and other processes. They contain various enzymes and serve as primary sites in the generation of cellular energy. Enzymes are proteins that accelerate the rate of specific chemical reactions. The term "metabolism" refers to all the chemical processes that occur within the body.
Ongoing research has determined that several metabolic disorders or inborn errors of metabolism may result in symptoms that mimic those associated with Reye syndrome (so-called "Reye-like diseases"). Metabolic disorders that may cause symptoms and findings similar to those seen in Reye Syndrome include certain urea cycle disorders (UCDs), organic acidurias, and abnormalities in fatty acid metabolism. (For information on such disorders, please see the "Related Disorders" section of this report below.)
Subdivisions of Reye Syndrome
Reye syndrome is a rare disorder that appears to affect males and females in relatively equal numbers. The disorder occurs almost exclusively in individuals younger than age 18 years. Most cases occur at about age 6, with most affected individuals ranging in age from approximately four to 12 years. However, there have been rare instances in which Reye syndrome has affected infants and young adults. Evidence suggests that children and adolescents in rural and suburban areas appear to be affected more frequently than those in urban areas.
The disorder was originally recognized as a distinct disease entity in 1963, when several cases were reported from the United States and Australia. Surveillance of Reye syndrome has indicated that the disorder tends to occur in outbreaks in association with viral infection (e.g., influenza B, varicella, various other viral infections) or may occasionally occur on a more sporadic basis, also in association with such viral infections.
The incidence of the disorder has dramatically declined in the United States beginning in the late 1980s. Approximately 200 to 550 cases were reported each year in the United States during 1974 to 1984. However, since 1988, fewer than 20 cases have been reported annually. Many researchers attribute the decline to increased public awareness concerning the potential association between Reye syndrome and the use of aspirin-containing preparations for certain viral infections and the recognition that some children suspected of having Reye syndrome actually have an inborn error of metabolism. Similar decreases in incidence rates have also been reported in the United Kingdom after public health warnings were issued.
particularly children from approximately age four to 12 years. In rare cases
Signs & Symptoms
infants or young adults may be affected. The disorder’s cause is unknown. However
there appears to be an association between the onset of Reye syndrome and the use of aspirin-containing medications (salicylates) in children or adolescents with certain viral illnesses
particularly upper respiratory tract infections (e.g.
Although any organ system may be involved
Reye syndrome is primarily characterized by distinctive
fatty changes of the liver and sudden (acute) swelling of the brain (cerebral edema). Associated symptoms and findings may include the sudden onset of severe
persistent vomiting; elevated levels of certain liver enzymes in the blood (hepatic transaminases); unusually high amounts of ammonia in the blood (hyperammonemia); disturbances of consciousness; sudden episodes of uncontrolled electrical activity in the brain (seizures); and/or other abnormalities
it is advised that such medications be avoided for individuals under age 18 years who are affected by viral infections such as influenza or chickenpox."